Therapeutic preparation



Patented Jan. 31, i939 2,145,799

UNITED TE PATENT OFFICE WEUTICPREPARATION I Horace M. Powell, Indianapolis, Ind., itssignor, to Eli Lilly and Company, Indianapolis, Ind., a corporation of Indiana No Application December 11, 1937,

' Serial No. 179,374 i x 3 Claims. (01. 101-85) It is the object of my invention to produce a with similarly infected controls not treated with modified sulfanilamide which has certain therathose preparations; whereas the sulfanilamide peutic advantages over si'ilfanilamide itself. alone or the quinine salt alone, in equal or even "Sulfanilamide, which is p-aminobenzenesulfongreater dosage, is not able to save such mice.

5 amide, has proven its efli'cacy asa'therapeutic In addition, it is found that in mice which agent in combatting certain bacterial infections. are infected with hemolytic streptococci of such However, it has not ordinarily proven effective high virulence that control mice died when inin the treatment of virus infections; and even in fectedwith one millionth of 1 cc. of the culture, the treatment of bacterial infections it requires the majority of the mice-survived when infected fairly large and repeated doses. In addition, with one hundredth of 1 cc. of the same culture 10 sulfanilamide itself has only-a very slight soluif they are also treated subcutaneously with (a) bility in water, of about 0.8%, so that when 5 mg. of sulfanilamide, or with (b) 4 mg. of an sulfanilamide is administered parenterally the equi-weight mixture of quinine salicylate and volume of liquid to be administered is sometimes sulfanilamide (which thus contains only 2 ms.

larger than is desirable. of sulfanilamide itself), or with (c) 5 mg. of an 15 I have discovered that by putting quinine salts equi-molecular mixture of quinine di-hydrochloand sulfanilamide together, I get a product which ride and sulfanilamide (which thus contains only is effective in the treatment of certain virus in- 1.5 m8- f s lfanilamidc itself). In these tests fections'; which is equally eif ctive with sulfaniltwo such doses of the drug were given each amide itself when administered in materially use. one an hour 'after the inoculation with so smaller dosages in terms of sulfanilamide com the culture and the other five hours after that tent; which has sufllciently greater water-soluinoculation; and the mice were observed for a bility than has sulfanilai'nide itself so that the p riod of two weeks'thereaiter. concentration of sulfanilamide proper in the The quinine-sulfanilamide preparations may solution is increased several fold; and which-is be e h r soluti 0! simpl mixtures 01 1 26 effective on either oral or parenteral adminisnine salt and sulfanilamide,-.or solutions in which tration, I q the desired separate amounts of a quinine salt The quinine salts which I use may be of variand sulfanilamide are dissolved; or they may be ous acids, such as a sulfate or a hydrochloride. s luti made by d 1vin8 iilystv-lline q i n 30 or a salicylate. sulfanilamide preparations. Two such crystal- 30 The quinine salt and the sulfanilamide may line preparations are quinine hydrochloride and be put together in any desired proportions, alsulfanilamide containing two molecules of lrvthough to get material benefit both ingredients drochloric acid, and quinine hydrochloride and should be present in substantial amount. For sulfanila nide containing three molecules of hya'e instance,-I have found it eflective with equal droehio i aciddn each s e w t e quinine parts by weight, as 1' uinin salieylate and hydrochloride and the sulfanilamide in molecular sulfanilamide, and also with equal molecular pr p rti n w h the whole forming homoequivalents, as of quinine di-hydrochloride and v seneous c ystals- Thp e ec c c ystal e prodsulfanilamide. Moreover, if a quinine hydrochlo- ,uc s e e prod c d by l er H- Stuart after I 4o ride or a quinine sulfate is used in such proporhad discovered the therapeutic value of mixtures 40 tions, the solubility of the product is so changed f ,quinin Salts nd l nil mi and are the that the concentration of the sulfanilamide subject-matter of his patent application Serial proper in water solution is markedly increased-#- No. 185,925, filed January 20, 1938. from about 0.8% to, about 3.0% in the case of I I claim its my inv n n: a product composed of equi-molecular propor-' I 1 .v A therapeutic product containing a quinine 5 tions of quininedi-hydrochloride and sulfanilsalt and sulfanilainide.

amide 1 2. A therapeutic product containing a quinine when suitable doses of these quinine-'sulfanile salt and sulfaniiamide in substantially equal pro amide preparations are administered hypoderportions by weight. 5b mically to mice infected with human influenza 3. A therapeutic product containing a quinine 5o 'virus,-it is found'that they have marked benesalt and sulfanilamide in substantially equiilcial therapeutic action against the eflect of that molecular proportions. virus, to the extent of saving the micragainst OR E P WELL- from1to10fataldosesofthevirus,ascompared Patent No. 2,115,799.

CERTIFICATE OF CORRECTION.

January 51, 1959. I HORACE M. POWELL. It is hereby certified that error appears in the above numbered patent I requining correction as ,follows: In the grant, lines 'gand 15, the name of th e assi gnee was erroneously written as "Eli Lily and Company" whereas said name should have been written as Eli Lilly and Company, as shown by the record of' assignments in this office; and that the said Letters Patent should be read with this correction thereinthat the same may'conform to the record of the case in the Patent Office.

Signed and sealed this 28th day of March, A. D. 1959.

Henry Van Arsdale ,(Seal) Acting Commissioner of Patents. 

